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Biomedical subjects

A M Jensen

Publications and source records attributed to A M Jensen.

At least 37 records · Page 2Linked to original sources
PubMed1995

Does cytomegalovirus predict a poor prognosis in Pneumocystis carinii pneumonia treated with corticosteroids? A note for caution.

OBJECTIVE: To examine the importance of cytomegalovirus (CMV) in bronchoalveolar lavage (BAL) fluid of patients with HIV-associated Pneumocystis carinii pneumonia (PCP) treated with adjunctive corticosteroids (CS). DESIGN: Analysis of clinical data during a 5-year period. SETTING: Department of infectious diseases where clinical and paraclinical data on patients suspected of having PCP have been sampled prospectively. PATIENTS: 148 consecutive patients with a first episode of PCP in a 5-year period. MAIN OUTCOME MEASURE: Vital status 3 months after diagnosis of PCP. RESULTS: Patients with PCP treated with adjunctive CS who had CMV cultured from BAL fluid had a two times higher mortality within 3 months from bronchoscopy than others (p = 0.08). This difference could not be explained by differences in CD4 count, PO2 or PCO2 at time of bronchoscopy. CONCLUSION: With the accepted usage of adjunctive CS in severe PCP, the role of CMV as a pulmonary copathogen may have changed. Active CMV infection may be an important cause of failing treatment of severe PCP in those treated with adjunctive CS.

AIDS-Related Opportunistic Infections↗
PubMed1994

Overexpression of mitogen-activated protein kinase kinase (MAPKK) and its mutants in NIH 3T3 cells. Evidence that MAPKK involvement in cellular proliferation is regulated by phosphorylation of serine residues in its kinase subdomains VII and VIII.

Mitogen-activated protein kinase kinase (MAPKK) is a dual specificity protein kinase that exhibits a high degree of specificity toward its downstream target, mitogen-activated protein kinase (MAPK). In this study, we used stable overexpression of MAPKK and its mutants in NIH 3T3 cells to study effects on downstream components of the MAPK signaling cascade and to correlate them to physiological responses. We have mutated the potential regulatory serine residue 222 to alanine (S222A) or to glutamate (S222E) and serines 212 and 218 together to alanine residues (S212A,S218A). Lysine 97 was mutated to alanine (K97A) to provide an inactive enzyme. Overexpression of the wild type MAPKK had no effect on any of the parameters examined. The K97A and S222A mutants served as dominant negatives by suppressing MAPKK, MAPK, and p90rsk activation in vivo. S222E enhanced all of these activities, and S212A,S218A had a small inhibitory effect. A similar trend was observed when cellular proliferation was examined and the different effects were accompanied by altered cellular shape. Taken together, our results demonstrate a direct linkage between the MAPK signaling pathway and the control of cellular proliferation and morphology and also establish that phosphorylation of serine 222 is essential for MAPKK activation together with the phosphorylation of an additional serine(s) (probably serine 218).

3T3 Cells↗
PubMed1994

[Pneumocystis carinii pneumonia in HIV-infected patients examined by bronchoscopy during the period 1989-1991].

We analyzed prospectively collected data from 211 HIV-infected patients who underwent bronchoscopy because of pulmonary symptoms during the period 1989-1991. We found an improvement in survival for patients diagnosed with Pneumocystis carinii pneumonia (PCP) in 1991 as compared to 1989 and 1990 (log rank test: p = 0.07). A significant decline in PO2 and CD4 cell count was observed in patients with PCP in the same period (p < 0.05 and 0.005 respectively). We suggest that the decline in CD4 cell count and in PO2 may reflect a change in Pneumocystis carinii transmission, and that the improved survival may be a result of altered treatment strategy of PCP.

AIDS-Related Opportunistic Infections↗
PubMed1993

Expression of glutamate receptor genes in white matter: developing and adult rat optic nerve.

We have identified the glutamate receptor genes expressed by developing and adult rat optic nerve. Results from PCR suggested that of the ionotropic glutamate receptor (GluR) gene family, only GluR1 and GluR3 subunits are expressed by optic nerve. However, Northern blot analysis demonstrated that only the GluR1 subtype is expressed at appreciable levels. In situ hybridization histochemistry of GluR1 was performed and a diffuse pattern of expression was observed in both postnatal day 15 and adult optic nerve. Restriction mapping of the GluR1 PCR product indicated the expression of the flip alternative splice version in optic nerve. The detected GluR1 message was not due to axons because no loss of expression was observed after the degeneration of axons. PCR analysis also revealed the presence of a metabotropic glutamate receptor in optic nerve.

Aging↗
PubMed1992

Human T-cell mitogen-activated protein kinase kinases are related to yeast signal transduction kinases.

Mitogen-activated protein (MAP) kinase kinases, intermediates in a growth factor-stimulated protein kinase cascade, are dual specificity protein kinases that specifically phosphorylate and activate MAP kinases in response to extracellular signals. Here, we report the cloning of two forms of cDNA that encode this protein from human T-cells. MKK1a encodes a protein with predicted molecular size of 43,439 Da. Overexpression of this clone in COS cells led to elevated levels of protein and phorbol ester-stimulated MAP kinase kinase activity, confirming that MKK1a encodes the predicted protein. MKK1b, which appears to be an alternatively spliced form of the MKK1a gene, encodes a protein with predicted molecular size of 40,745 Da. Northern analysis revealed that the MKK1 cDNA hybridizes with a single 2.6-kilobase mRNA species in all human tissues examined. Sequence comparison shows homology to a group of yeast kinases that participate in signal transduction and to subdomain XI of other dual specificity kinase.

Amino Acid Sequence↗
PubMed1992

Purification and characterization of mitogen-activated protein kinase activator(s) from epidermal growth factor-stimulated A431 cells.

Two peaks of mitogen-activated protein (MAP) kinase activator activity are resolved upon ion exchange chromatography of cytosolic extracts from epidermal growth factor-stimulated A431 cells. Two forms of the activator (1 and 2) have been purified from these peaks, using chromatography on Q-Sepharose, heparin-agarose, hydroxylapatite, ATP-agarose, Sephacryl S-300, Mono S, and Mono Q. The two preparations each contained one major protein band with an apparent molecular mass of 46 or 45 kDa, respectively, on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Evidence identifying the MAP kinase activators as the 46- and 45-kDa proteins is presented. Using inactive mutants of MAP kinase as potential substrates, it was found that each preparation of MAP kinase activator catalyzes phosphorylation of the regulatory residues, threonine 188 and tyrosine 190, of Xenopus MAP kinase. These results support the concept that the MAP kinase activators are protein kinases. These MAP kinase kinases demonstrate an apparent high degree of specificity toward the native conformation of MAP kinase, although slow autophosphorylation on serine, threonine, and tyrosine residues and phosphorylation of myelin basic protein on serine and threonine residues is detected as well.

Animals↗
PubMed1991

Correlates of concern in parents of high-risk infants at age five.

Parents whose children have experienced a high-risk birth may be in double jeopardy due to the biomedical effects of the birth trauma as well as parent perceptions and feelings regarding medical vulnerability and the subsequent impact on caregiving. The present study determined whether the developmental, social, and medical concerns reported by 223 parents of high-risk infants at age 5 were congruent with the child's medical history and developmental performance at age 5. Results indicated that parents with the highest levels of developmental, social, and medical concerns had children with lower birth weights who were born earlier and spent longer periods of time in the hospital at birth. These children also had lower outcomes on the cognitive ability measures at age 5, and were more likely to demonstrate potential behavior problems. Present findings suggest the degree of concern reported by parents of high-risk infants is congruent with the birth history and the developmental status of their child.

Adaptation, Psychological↗
PubMed1991

Differential intracellular calcium responses to glutamate in type 1 and type 2 cultured brain astrocytes.

Fluorescence image analysis using the calcium indicator fluo-3 was used to examine changes in [Ca2+]i induced by glutamate in mixed glia populations cultured from neonatal rat brains. [Ca2+]i responses were correlated with glia type by performing immunohistochemistry using markers specific for type 1 and type 2 astrocytes on the same cells used in the imaging experiments. Glutamate (30-500 microM) induced two markedly different [Ca2+]i responses in the two astrocyte types: the response in type 1 astrocytes consisted of an initial fast transient followed by varying degrees of oscillations, whereas the predominant response in type 2 astrocytes was a slow rise in [Ca2+]i to a more or less sustained and nonoscillatory level. In some type 2 astrocytes, an initial spikelike transient similar to that in type 1 astrocytes was observed; the overall size of the spike, however, was smaller than in type 1 astrocytes. Two agonists for the ionotropic glutamate receptor, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) and kainate, elicited a 6-cyano-7-dinitroquinoxaline-2,3-dione (CNQX)-sensitive, external Ca(2+)-dependent, sustained [Ca2+]i rise in type 2 but not type 1 astrocytes. The initial spike in type 2 astrocytes was less dependent on external Ca2+ and not blocked by CNQX. [Na+]i as measured by the Na(+)-fluorescence dye SBFI, was elevated by kainate in both astrocyte types, though the increase was larger in type 2 astrocytes. This increase was reduced by CNQX, suggesting this [Ca2+]i increase was mediated, at least in part, by ionotropic glutamate receptors. The results are discussed in terms of the relative distribution of two classes of glutamate receptors on these two astrocyte types: one, the ionotropic class, is linked directly to an ion channel, and the other, the metabotropic class, induces internal mobilization of Ca2+ via inositol phospholipid hydrolysis.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1990

Global assessment of patients--a bedside study. II. Inter-observer variation and frequency of clinical findings.

Three physicians independently assessed 201 hospital in-patients for the presence of 10 basic physical characteristics, and made an overall assessment of whether or not the patients appeared ill. There were significant differences between the physicians in the average number of observations recorded for each patient (P less than 0.001). There was a significant difference (P less than 0.05) between the physicians regarding the number of positive diagnoses of anaemia, abnormal nutritional state, breathing difficulties and the overall assessment. Inter-observer variation was estimated by a pairwise comparison of the three physicians. Overall agreement rates ranged from 0.65 for abnormal nutritional state to 0.99 for presence of pain. After adjusting for random agreement, kappa values between 0.09 (elevated body temperature) and 0.88 (consciousness impaired) were found. No tendency towards a higher level of agreement in the overall assessment than in the basic findings was observed.

Diagnosis↗
PubMed1990

Epidemiology of bovine virus diarrhoea virus.

A better understanding of the epidemiology and pathogenesis of bovine virus diarrhoea virus (BVDV) has emerged in recent years. Fetal infections and in particular those resulting in birth of persistently infected calves are of central importance for the epidemiology of BVDV. A prevalence of persistently infected, viraemic animals of about 1% is found in Denmark and elsewhere by examination of randomly collected blood samples. A recent field study shows that 53% of randomly selected herds in an area in Denmark where BVDV is endemic had one or more persistently infected animals. Persistently infected cows may breed and will always transmit the infection to the calf. Such familial occurrence of persistent infection seems to be a fairly common phenomenon. Persistently infected cattle are important sources of infection to other cattle. Transiently infected cattle following experimental exposure will usually not transmit the infection by contact but this may not always apply to cattle after natural infection. Knowledge of the occurrence and potential for spread of virus from persistently infected bulls is reviewed. Virus is excreted with semen of both persistently and transiently infected bulls and BVDV may be transmitted by use of infected semen for insemination. The potential for spread of the infection through embryo transfer should be avoided by the use of adequate testing and controls.

Animals↗
PubMed1990

Fluorescence measurement of changes in intracellular calcium induced by excitatory amino acids in cultured cortical astrocytes.

Population response of [Ca2+]i in cultured cortical astrocytes to excitatory amino acids was measured at room temperature using the calcium-sensitive dye fura-2. Quisqualic acid (QA), glutamate (Glu), and kainic acid (KA) caused a peak increase in [Ca2+]i in the order QA greater than Glu greater than KA. No response to N-methyl-D-aspartic acid (NMDA) was observed whether or not Mg2+ was present externally. Both QA and Glu (100 microM) frequently elicited a decaying oscillatory [Ca2+]i response during sustained agonist application; the period of oscillations initially was 23.5 sec and increased as the response was damped. Comparatively, the [Ca2+]i response to KA was nonoscillatory. Both responses to Glu and KA were reduced slightly by antagonist gamma-D-glutamylaminomethyl-sulfonic acid (1 mM), but virtually were abolished by kynurenic acid (3 mM). Replacement of external Na+ by choline had no significant effect on the Glu response. Removal of external Ca2+ reduced the peak response to QA, Glu, and KA to 40, 34, and 18%, respectively; and markedly reduced the degree of QA- and Glu-induced [Ca2+]i oscillations. Pretreatment with phorbol esters, a potent activator of protein kinase C, blocked the [Ca2+]i response to Glu but not KA. It is concluded that cortical astrocytes express Glu receptors of the non-NMDA type in culture and that receptor activation leads to Ca2+ influx and release of internal Ca2+. Mobilization of Ca2+ apparently occurs via the known Glu-mediated hydrolysis of inositol lipids, which may come under negative-feed-back control by protein kinase C activation. Oscillatory [Ca2+]i signaling offers the possibility of a dynamic population response in an electrically coupled glial network.

Amino Acids↗
PubMed1989

Reproducibility in the analysis of multigated radionuclide studies of left ventricular ejection fraction.

The authors determined the reproducibility (the standard deviation [SD]) in the analysis of multigated radionuclide studies of left ventricular ejection fraction (LVEF). Radionuclide studies from a consecutive series of 38 patients suspected of ischemic heart disease were analyzed independently by four nuclear medicine physiologists and four laboratory technicians. Each study was analyzed three times by each of the observers. Based on the analyses of the eight observers, the SD could be estimated by the use of a variance component model for LVEF determinations calculated as the average of the analyses of an arbitrary number of observers making an arbitrary number of analyses. This study presents the SDs for LVEF determinations based on the analyses of one to five observers making one to five analyses each. The SD of a LVEF determination decreased from 3.96% to 2.98% when an observer increased his number of analyses from one to five. A more pronounced decrease in the SD from 3.96% to 1.77% was obtained when the LVEF determinations were based on the average of a single analysis made by one to five observers. However, when dealing with the difference between LVEF determinations from two studies, the highest reproducibility was obtained if the LVEF determinations at both studies were based on the analyses made by the same observer. No significant difference was found in the reproducibility of analyses made by nuclear medicine physicians and laboratory technicians. Our study revealed that to increase the reproducibility of LVEF determinations, special efforts should be made to standardize the outlining of the end-systolic region interest.

Adult↗
PubMed1989

Global assessment of patients--a bedside study. I: The influence of physical findings on the global assessment.

Three physicians selected ten basic physical findings for a study of diagnostic decision making in the global assessment of patients. The physicians independently examined 201 hospital in-patients for the presence of each of the findings and concluded their assessment with a global evaluation of whether the patient appeared ill. Each of the ten findings were used by at least one of the physicians in his overall assessment of the patient. All the observers considered 'looking older than age', 'trouble with breathing', 'cyanosis', and 'anaemia' important, but disagreed in their use of the remaining findings (P less than 0.01). Agreement in the global clinical assessment is an essential prerequisite to uniformity in the approach to the patient.

Adolescent↗
PubMed1988

Transmission of bovine virus diarrhoea virus (BVDV) by artificial insemination (AI) with semen from a persistently-infected bull.

Twelve heifers that did not have antibodies to bovine virus diarrhoea virus (BVDV) were inseminated with semen from a bull that was persistently infected with the virus and contained 10(4.0)-10(6.5) TCID50 0.1 ml-1. All 12 became infected, as indicated by seroconversion within 2 weeks of insemination. Four control heifers were inseminated with virus-free semen. The virus was not transmitted to these animals in spite of close contact with the heifers inseminated with the infected semen. All the heifers became pregnant and gave birth to clinically normal calves at term. However, one calf was born persistently infected with BVDV. After the birth of this persistently-infected calf the control heifers and their calves seroconverted. The study demonstrates that BVDV may be transmitted in cattle by artificial insemination (AI). Therefore entry of persistently-infected animals into AI centres should be prevented.

Animals↗
PubMed1986

Interobserver variation in the detection of metastases on liver scans.

Two specialists in nuclear medicine and two trainees independently read 106 liver scans for abnormalities suggestive of metastases. The four observers made a positive diagnosis with a significantly different frequency. The overall agreement between pairs of observers was 0.83-0.87. After adjusting for the expected chance agreement, kappa-values between 0.66 and 0.74 were obtained. No difference was found in the level of agreement between the two specialists or between the two trainees. After a consensus conference where the observers tried to unify their diagnostic interpretation, another 106 scans were read for abnormalities suggestive of metastases. The conference did not increase the level of agreement. Scintigraphic lesions that especially imply a risk of disagreement are pointed out.

Colloids↗
PubMed1986

A critical evaluation of the clinical diagnosis of anemia.

Three physicians independently assessed whether 180 medical or surgical inpatients were anemic. The assessments were based on inspection of skin, nail beds, and conjunctivae. The observers made a positive diagnosis with significantly different frequency. Overall agreements between pairs of observers were 0.76-0.87. Agreement on negative diagnoses was higher than agreement on positive diagnoses. The overall agreements were adjusted for chance agreement, and kappa values which ranged from 0.23-0.47 were obtained. The overall accuracy of the clinical diagnoses was determined with the blood hemoglobin concentration as the "true" standard. For the three observers, the overall accuracy ranged from 0.78-0.79, the predictive value of a positive diagnosis ranged from 0.51-0.61, the predictive value of a negative diagnosis ranged from 0.81-0.84, the sensitivity ranged from 0.27-0.44, and the specificity ranged from 0.88-0.95. For each observer, the probability of detecting anemia was estimated as a function of the blood hemoglobin concentration. Compared with the "true" diagnosis, the observers were reluctant to call a patient anemic, and even in patients with the lowest blood hemoglobin concentrations, the expected probability of detecting anemia did not exceed 0.75.

Adolescent↗